Multi-disciplinary studies on diffuse degenerative diseases of the human brain, in particular those affecting children, have led to the delineation of the neuronal ceroid-lipofuscinoses, a group of diseases characterized by the accumulation of intracellular autoflourescent lipopigments, particularly severe in cerebral neurons. This pigment formation is due to a increased rate of peroxidation of polyunsaturated fatty acids and damages the affected cells, producing neuronal dysfunction and loss. Several clinically and presumably genetically different conditions make up the neuronal ceroid-lipofuscinoses. However, the various diseases are quite similar with respect to the pathology and very similar to a disease in inbred English Setters inherited as an autosomal recessive. Practically all patients with neuronal ceroid-lipofuscinosis as wel as all affected dogs reveal a profound deficiency of a PPD-linked peroxidase in white cells but not in the tissues. Studies are proposed to investigate the role of peroxidation and peroxidases in the pathogenesis of neuronal ceroid-lipofuscinosis.